Non Animal Testing, Alternative Test Methods, In Vitro Toxicology, IIVS | Documents & Resources
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Documents & Resources

Video: The 3T3 Neutral Red Uptake Phototoxicity Test

October 31, 2018

This training video explores a cell-based method for assessing Phototoxicity — or the potential for chemicals to cause damage after being exposed to light.  The method is used widely around the world by many industries, including the cosmetics and pharmaceutical sectors. Disclaimer:  Please note that the procedures shown in this video were for demonstration ...

Non-animal Vaginal Irritation Method Admitted into the US FDA Medical Devices Development Tool (MDDT)

October 18, 2018

FDA’s recently launched Predictive Toxicology Roadmap calls for the optimization of non-animal methods for the safety evaluation of drugs, consumer products and medical devices. We have created an Industry Consortium comprised of manufacturers of personal lubricants/vaginal moisturizers and companies interested in the advancement of animal alternatives working collaboratively with stakeholders and the US FDA to develop an in vitro testing approach that could be used in place of the rabbit vaginal irritation (RVI) in pre-market submissions.

How the Good In Vitro Method Practices Guidance Document Can Help Implement New Toxicological Approaches: A Case Study in China

October 17, 2018

Currently China is striving to adopt and implement non-animal, including in vitro, testing approaches for the safety assessment of cosmetics and ingredients.  Collaborative efforts between industry and the Institute for In Vitro Sciences (IIVS, Gaithersburg, USA) have focused on the transfer of several OECD Test Guideline methods to government laboratories in China and have supported the creation of an in vitro toxicology testing laboratory within the Zhejiang Institute for Food and Drug Control (Hangzhou, China).  Recently BASF SE (Ludwigshafen, Germany) and IIVS have partnered to introduce a cell based in vitro skin sensitization test, LuSens, into China using the principles of GIVIMP as a standard.  This case study exemplifies the practical way in which the GIVIMP guidance can assist interested parties in the development, transfer and establishment of in vitro approaches.

Tiered In Vitro Testing Strategy For Assessing The Ocular and Dermal Irritation/Corrosion Potential of Pharmaceutical Compounds

July 23, 2018

Read our latest publication with Bristol-Myers Squibb regarding a tiered testing strategy for occupational hazards of pharmaceutical intermediates now published in the Cutaneous and Ocular Toxicology Journal. Irritation reactions are a frequently reported occupational illness. The potential adverse effects of pharmaceutical compounds (PCs) on employees' eyes and skin can now be assessed using validated in vitro methods. Our overall aim is to reduce animal testing by replacing the historically utilized in vivo test methods with validated in vitro test methods which accurately determine the ocular and dermal irritation/corrosion potential of PCs to inform worker safety within the pharmaceutical space. BMS and IIVS have therefore conceptualized and internally qualified a tiered in vitro testing strategy to inform occupational hazards regarding eye and skin irritation and corrosivity of PCs. which is based on three Organisation for Economic Co-operation and Development (OECD) in vitro methods (OECD TG 435, OECD TG 437, OECD TG 439.) Read the full article.  

Next-Generation Tobacco and Nicotine Products: Substantiating Harm Reduction and Supporting Tobacco Regulatory Science

June 21, 2018

A framework for the assessment of novel next-generation tobacco and nicotine products with the potential to reduce health risks compared with cigarettes should integrate scientific studies incorporating nonclinical, clinical, and population studies approaches.  These products should have lower emissions and exhibit reduced biological effects compared with those of cigarettes, ideally approaching those of smoking cessation.  The products should also be acceptable cigarette alternatives for current smokers, while not appealing to nonsmokers or former smokers.  Validating harm reduction and promoting regulatory acceptance of the assessment methods require a collaborative approach by industry, independent reviewers, the public health community, and regulatory agencies.  This article summarizes the science and approaches applied and considered to substantiate tobacco harm reduction in the light of regulatory requirements. Read the full article.  

Characterization of a Vitrocell VC1 Using Nicotine Dosimetry: An Essential Component Toward Standardized In Vitro Aerosol Exposure of Tobacco and Next Generation Nicotine Delivery Products

June 21, 2018

The U.S. Food and Drug Administration has regulatory authority over tobacco products, including conventional cigarettes and next generation products (NGPs) such as e-cigarettes and tobacco heating products (THPs).  There is a desire by the industry, regulators and animal protection organizations to incorporate non-animal test methods for tobacco product and NGP assessment.  When assessing respiratory effects in vitro, reliable exposure systems that deliver aerosols to cellular/tissue cultures (such as human reconstructed airways or lung slices) at the air–liquid interface are needed.  Using nicotine dosimetry, we report the characterization of a Vitrocell VC1 in our laboratories (IIVS, USA).  Nicotine, generated from a 3R4F reference cigarette or NGP (e-cigarette and THP) aerosols at source and the exposure interface (culture media), was assessed using ultra-high-performance liquid chromatography–tandem mass spectrometry.  These data were compared to published dosimetry data for the same products, generated at a different laboratory (BAT R&D, Southampton, UK), on different exposure systems (VC10 and Borgwaldt RM20S) to confirm repeatability. Read the full article.  

Evaluation of Phototoxicity of Ocular Medical and Combination Devices

March 28, 2018

To address ocular device induced phototoxicity, an in vitro 3T3 Neutral Red Uptake Phototoxicity test (OECD 432) for chemicals has been modified. Soft contact lenses formulated with three different photo-absorbing compounds and chemical solutions of these compounds were evaluated.

The Assessment of Phototoxicity Using the 3T3 Neutral Red Uptake (NRU) Phototoxicity Assay and a Modified Photo-Direct Peptide Reactivity Assay (DPRA)

March 28, 2018

Alternative methods, including the validated 3T3 Neutral Red Uptake (NRU) Phototoxicity assay (OECD TG 432) may be used as a pre-clinical test to address phototoxicity. Currently, there are no validated alternative test methods to identify photoallergens; however, there are several validated alternative test methods to address skin sensitization, including the Direct Peptide Reactivity Assay (DPRA) (OECD 442C). To address photoallergy, we utilized the 3T3 Phototoxicity assay in combination with a modified photo-DPRA assay to determine if these assays were able to 1) identify compounds with phototoxicity potential and 2) discriminate between photoirritants and photoallergens.

Human In Vitro Models for Respiratory Toxicology: Evaluation of Goblet Cell Hyperplasia, Mucus Production, and Ciliary Beating Assays

March 28, 2018

Robust non-animal models and assays for pulmonary toxicology are required to make competent product development and risk assessments for new materials requiring toxicity testing. Three in vitro assays (goblet cell hyperplasia , ciliary beat frequency , and MUC5AC quantitation) were evaluated for performance and reproducibility. To assess these assays, 6 laboratories contributed data using a common protocol utilizing IL-13 as an inducer of adverse mucociliary-relevant tissue changes. MatTek EpiAirway™ and Epithelix MucilAir™ 3D tissue models were used to evaluate endpoints using histology for GCH, software-based applications, Cilia FA and SAVA, for CBF, and ELISA assay for MUC5AC.